Dehydrative Coupling of Carboxylic Acids with Amines in the Presence of Sodium Azepane-1-carbodithioate

Abstract The reaction of a carboxylic acid with an amine in the presence of a catalytic carbodithioate affords the corresponding amide under thermal conditions, excluding the requirement for stoichiometric coupling reagents. The high-yield preparation of amides in the presence of sodium azepane-1-carbodithioate, which can be readily prepared, demonstrates that this agent does not behave as a simple nucleophile but rather plays a critical role in acyl activation and transfer. The advantages of the developed simple catalytic method include minimization of reagents, the ability to operate in a solvent-free environment in many cases, minimal solvent requirement, high product yield, and applicability for scale-up in the synthesis of amides. This method allows for the successful use of various aliphatic and/or aromatic substrates as well as some functionalized carboxylic acids. The study also provided mechanistic insights into the amidation process through Fourier transform infrared analysis and density functional theory calculations.