Microwave-assisted Synthesis of 2-Substituted 4,5,6,7-Tetrahydro-1,3-thiazepines from 4-Aminobutanol

A general procedure for the synthesis of 2-substituted tetrahydro-1,3-thiazepines is presented, by MW-assisted cyclization of 4-thioamidobutanols. The acyclic precursors were prepared in high overall yields by an expeditious three step diacylation/thionation/deprotection sequence from 4-aminobutanol. Microwave assisted ring closure of 4-thioamidoalcohols promoted by trimethylsilyl polyphosphate (PPSE) in solvent-free conditions allowed for the synthesis of several hitherto unreported seven-membered iminothioethers bearing 2-aryl, alkenyl, aralkyl and alkyl substituents. The cyclodehydration reaction is likely to involve a S N 2-type displacement and affords good to excellent yields of the desired heterocycles in very short reaction times.