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Updated: Aug 16, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
A Facile Synthesis of 2-Oxazolines via Dehydrative Cyclization Promoted by Triflic Acid
Tao Yang1,2, Chengjie Huang1,2, Jingyang Jia1,2
1Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, China.
Abstract:
2-oxazolines are common moieties in numerous natural products, pharmaceuticals, and functional copolymers. Current methods for synthesizing 2-oxazolines mainly rely on stoichiometric dehydration agents or catalytic dehydration promoted by specific catalysts. These conditions either generate stoichiometric amounts of waste or require forcing azeotropic reflux conditions. As such, a practical and robust method that promotes dehydrative cyclization while generating no byproducts would be attractive to oxazoline production. Herein, we report a triflic acid (TfOH)-promoted dehydrative cyclization of N-(2-hydroxyethyl)amides for synthesizing 2-oxazolines. This reaction tolerates various functional groups and generates water as the only byproduct. This method affords oxazoline with inversion of α-hydroxyl stereochemistry, suggesting that alcohol is activated as a leaving group under these conditions. Furthermore, the one-pot synthesis protocol of 2-oxazolines directly from carboxylic acids and amino alcohols is also provided.
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