Amide Synthesis from Thiocarboxylic Acids and Amines by Spontaneous Reaction and Electrosynthesis

Amide bond formation is one of the most important basic reactions in chemistry. A catalyst‐free approach for constructing amide bonds from thiocarboxylic acids and amines was developed. The mechanistic studies showed that the disulfide was the key intermediate for this amide synthesis. Thiobenzoic acids could be automatically oxidized to disulfides in air, thioaliphatic acids could be electro‐oxidized to disulfides, and the resulting disulfides reacted with amines to give the corresponding amides. By this method, various amides could be easily synthesized in excellent yields without using any catalyst or activator. The successful synthesis of bioactive compounds also highlights the synthetic utility of this strategy in medicinal chemistry. No catalyst required: A catalyst‐free approach for constructing amide bonds from thiocarboxylic acids and amines is developed. Mechanistic studies show that the disulfide is the key intermediate. Thiobenzoic acids can be automatically oxidized to disulfides in air, thioaliphatic acids can be electro‐oxidized to disulfides, and the resulting disulfides react with amines to give the corresponding amides.