A novel method for N-(hetero)arylamide synthesis based on rarely explored amine activation, rather than classical acid activation, is developed. The key component of the new method is activation of the amine by conversion into the corresponding isothiourea using a three-component reaction with an isocyanide and an S-phenyl benzenethiosulfonate, followed by reaction with a carboxylic acid under base metal catalysis. The scope of the method is studied using variety of acids and amines as starting materials for the amide synthesis. In particular, it is shown that the challenging sterically hindered amides can efficiently be prepared by the newly developed method. The mechanism of the new method was studied. As a demonstration of the power of synthetic methodology towards the relevant targets, a fungicide boscalid and an anti-arrhythmic drug Tocainide was accomplished. Finally, in order to improve the sustainability of the new method, the recycling of the side product was demonstrated.
As a major dissemination result, 3 scientific publications have been produced (2 are published, one accepted for publication at the moment of submittign the project report) . In order to communicate about the project to the public, a project blog on a social media was maintained (see the link below). A video was published on You Tube: https://youtu.be/uQ4xvkRN00s
. Both these actions target broad public and university students. A poster presentation at one of the Kekule cycle evenings organized at the University of Antwerp within the Flemish Government Initiative “Action Plan on Science Information and Innovation” targeted chemistry professionals in the broad sense, including University alumni active in industry and public sector.