Synthesis of 6-halogen-substituted 2-methylene-2,3-dihydro-1,4-oxazepine 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: 2017

Öğrenci: ÖZGE İBİŞ

Danışman: METİN ZORA

Özet:

Heterocyclic compounds are important since they are present in life naturally or synthetically. Among heterocyclic compounds, seven-membered 1,4-oxazepines are giving more attention than ever due to their wide range of biological and medicinal activities. There are many studies about their synthesis and new ones continue to appear. In this study, synthesis of halogen-substituted 1,4-oxazepine derivatives was investigated, which may have potential for biological studies. For this purpose, α,β-alkynic ketone derivatives were prepared by the reaction of aryloyl chlorides with terminal alkynes in the presence of a Pd catalyst. After that, by conjugate addition reaction between α,β-alkynic ketones and propargylamine, 23 N-propargylic β-enaminone derivatives were synthesized. Secondly, α-halogen substitution reactions of N-propargylic β-enaminone derivatives were studied with NCS and Selectfluor® for chlorine and fluorine substitution, respectively. By these reactions, 23 novel α-chloro-substituted and 5 novel α-fluoro-substituted N-propargylic β-enaminone derivatives were synthesized in good yields. In the final stage of this study, electrophilic cyclizations of halogen-substituted N-propargylic β-enaminones were investigated. When treated with zinc chloride by refluxing chloroform, they afforded 6-halo-substituted 1,4-oxazepines in good yields. In conclusion, 23 novel chloro-substituted and 5 novel fluoro-substituted 1,4-oxazepine derivatives were synthesized.