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Synthesis of 1,4-Thiazepines
Yilmaz Kelgokmen1, Metin Zora1
1Department of Chemistry , Middle East Technical University , 06800 Ankara , Turkey.
Abstract:
An efficient, general, and unprecedented methodology for the synthesis of 2-methylene-2,3-dihydro-1,4-thiazepines from N-propargylic β-enaminones is described. Initially, N-propargylic β-enaminones were thionated with Lawesson's reagent in good to high yields, and then the resulting N-propargylic β-enaminothiones were subjected to electrophilic cyclization. When treated with zinc chloride in refluxing chloroform, N-propargylic β-enaminothiones underwent electrophilic cyclization to yield 2-methylene-2,3-dihydro-1,4-thiazepines in good to high yields. A general trend was observed for all N-propargylic β-enaminothiones, and the cyclization proceeded with high efficiency and large functional group tolerance. This process is also applicable to the cyclization of internal alkyne-tethered N-propargylic β-enaminothiones. This operationally simple and facile method may represent a very rapid entry to a library of functionalized 1,4-thiazepines in the area of pharmaceuticals.
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