Access to 4-(pyridin-2-yloxy)-1,2,4-thiadiazol-5(4H)-ones via an amidoxime O-heteroarylation/cyclization reaction sequence

Abstract

A synthetic method was developed for the preparation of O-pyridylamidoximes in good preparative yields (up to 99%) by a reaction of the corresponding amidoximes with pyridine/quinoline N-oxides in the presence of PyBroP as an activator. Substituents in the used arylamidoxime had little effect on the yield of the target products, whereas the N-oxide structure had the greatest effect. O-Pyridyl-substituted amidoximes undergo an unusual condensation with (chlorocarbonyl)sulfenyl chloride. This transformation provides access to previously unreported 1,2,4-thiadiazol-5(4H)-ones functionalized at the N4 atom of the heterocycle by a pyridine moiety. Structural analysis of the products, combined with DFT theoretical calculations, allowed us to propose a reaction mechanism involving a key acylpyridinium intermediate.