Synthesis of 2-Dialkylaminomethyl-1,4-benzoxathians

Some sulfur analogs of 2-dialkylaminomethyl-1,4-benzo-dioxans were synthesized and evaluated as aL-adrenergic blocking agents to observe the effect of substitution of sulfur for oxygen on adrenolytic activity. Reaction of 2-hydroxybenzenethiol with dialkyl-2,3-dibromopropylamines resulted in the formation of 2-dialkylaminotnethyl-1,4-benzoxathians. The structure of these compounds was proven by the use of NMR spectroscopy. In an effort to explore other synthetic routes, 2-hydroxybenzenethiol was reacted with ethyl 2,3-dibromopropionate to give an ethyl 1,4-benzoxathiancarboxylate, which was reduced to the corresponding alcohol and converted via the tosylate to various dialkylaminomethyl-1,4-benzoxathians. A study of the NMR spectra indicated these compounds were 2-dialkylaminomethyl-1,4-benzoxathians. Pharmacological evaluations using the rat vas deferens preparation demonstrated that the benzoxathians are partial agonists revealing a fundamental difference from the corresponding oxygen analogs, the benzodioxans, which are competitive antagonists to epinephrine.