Thieno [2,3-d]isothiazoles were synthesized as potential plant activators. Based on previously reported thienothiadiazole plant activators, one ring nitrogen was eliminated from the bicyclic motif in order to extend structure activity relationship information. Thieno [2,3-d]isothiazoles bearing different functional groups were prepared starting from readily available 3,4-dibromothiophene. Introduction of an oxime and a methylthio group in positions 1 and 2 of the thiophene system set the stage for cyclization, which occurred spontaneously after converting the oxime into the more reactive oxime ester in the presence of methanesulfonyl chloride.
Reduction of nitrothiocyanatothiophene 2, available via nucleophilic substitution from the corresponding bromo compound 1, gave thienothiazole 3 in excellent yield. Conversion of the amino functionality under Sandmeyer conditions gave access to halo compounds 4 as key intermediates for the subsequent introduction of sulfur, nitrogen, and oxygen nucleophiles. An unexpected side-reaction was observed when DMF was used as solvent and a mechanism for the introduction of a dimethylamino group is proposed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.