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

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Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Kimya Bölümü, Türkiye

Tezin Onay Tarihi: 2018

Öğrenci: ELİF SEREL YILMAZ

Danışman: METİN ZORA

Özet:

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.