Synthesis of alkynyl-substituted pyrrole and 1,4-thiazepine derivatives

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2018
Yılmaz, Elif Serel
Heterocyclic compounds have a great importance in medicinal chemistry because of their presence in a number of pharmaceuticals. Among them, pyrroles and 1,4-thiazepines play a vital role in pharmaceutical chemistry because of their presence in a number of bioactive molecules and natural products. For this reason, the development of new synthetic methods for the synthesis of these compounds has attracted much attention. Recently, the cyclization of functionally-substituted alkynes has emerged as a valuable tool in the preparation of various heterocyclic and carbocyclic compounds. In this regard, N-propargylic β-enaminones have proven to be useful. In this study, we have anticipated that the cyclizations of N-(2,4-pentadiynyl)-β-enaminones would produce biologically important alkynyl-substituted pyrrole and 1,4-thiazepine derivatives. In the first part of this study, we have shown that conjugate addition of propargylamine to α,β-alkynic ketones followed by the coupling of the resulting N-propargylic β-enaminones with terminal alkynes, yields N-(2,4-pentadiynyl)-β-enaminones. When treated with a base such as sodium hydride, N-(2,4-pentadiynyl)-β-enaminones afforded alkynyl-substituted pyrrole derivatives. In the second part of this study, we have shown that when treated with Lawesson’s reagent, β-enaminones produced in situ N-(2,4-pentadiynyl)-β-enaminothiones that underwent intramolecular cyclization immediately to afford 2-(2-propyn-1-ylidene)-2,3-dihydro-1,4-thiazepines in good yields in one-pot manner. In conclusion, 7 novel alkynyl-substituted pyrrole and 12 novel 1,4-thiazepine derivatives were synthesized.

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Citation Formats
E. S. Yılmaz, “Synthesis of alkynyl-substituted pyrrole and 1,4-thiazepine derivatives,” M.S. - Master of Science, Middle East Technical University, 2018.