Mechanochemical Synthesis of 5-Amino-4-Cyanoxazoles

Abstract

A mechanochemical methodology for the preparation of 5-amino-4-cyanoxazoles through the reaction of 2-amido-3,3-dichloroacrylonitriles with primary or secondary aliphatic amines (or their respective salts) in the presence of dipotassium phosphate is reported. The process is carried out by processing the mixture of starting materials in a mixer mill, with ethanol used as a liquid-assisted grinding additive. Dipotassium phosphate serves as a cost-efficient and non-toxic inorganic base, ensuring 100% carbon economy of the process. The reaction produces the corresponding oxazole products with up to 97% yield in just 10 min. However, preparative scope of the method is restricted to highly nucleophilic and sterically unobstructed primary and secondary aliphatic amines. Aromatic amines display low reactivity at room temperature. For instance, indoline achieves only 43% conversion to its oxazole product after 3 h.