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

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.


Synthesis of highly substituted alkynylpyridines and development of new methodologies for the synthesis of 1,4-oxazepines, 1,4-thiazepines and 5-methylpyridines /
Kelgökmen, Yılmaz; Zora, Metin; Department of Chemistry (2018)
Convenient syntheses of pyridines, 1,4-oxazepines and 1,4-thiazepines have become an important research area among organic chemists since they constitute scaffolds of many medicinal substances. Recently, N-propargylic β-enaminones have been widely used for the facile synthesis of potent biologically active heterocycles. Many research groups have focused on the proper synthesis of various heterocycles by using N-propargylic β-enaminones. One of the such recent reports using these precursors is the formation ...
Synthesis of 6-halogen-substituted 2-methylene-2,3dihydro-1,4-oxazepine derivatives
İbiş, Özge; Zora, Metin; Department of Chemistry (2017)
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 ...
Synthesis of new pyrrole derivatives from npropargylic β-enaminones
Kanova, Nilay; Zora, Metin; Department of Chemistry (2020)
Heterocyclic compounds are a momentous area of synthetic organic chemistry because of their existence in bioactive molecules. Pyrroles, which are one of the most important classes of heterocyclic compounds, have great importance in pharmaceutical chemistry due to their biological activities. Having these characteristics makes them drawn attention of most chemists to develop new methodologies for the synthesis of pyrroles. Recently, the cyclization of Npropargylic β-enaminones has been used for the synthesis...
Synthesis of indole fused heterocyclic compounds
Kaptı, Tolga; Balcı, Metin; Department of Chemistry (2013)
Nitrogen containing heterocyclic compounds show wide range of biological activities so their syntheses have always been attractive area in organic chemistry. Indole derivatives, which are one of the important example of these biological active compound, are precursors to many pharmaceuticals. The aim of this research is to develop new synthetic methodologies leading to the synthesis of new derivatives of pyrimidoindole and quinoline, which have been found to show important biological activities. In this stu...
Synthesis of 2,3-disubstituted thiophenes from ketoalkynes
Vatansever, Erol Can; Balcı, Metin; Department of Chemistry (2013)
Synthesis of thiophene containing compounds are of particular interest in synthetic organic chemistry. Besides the importance for synthetic organic chemistry, thiophene derivatives are used in applied research such as drug synthesis and study of functional materials. In this thesis, a new methodology for developing of 2,3-disubstituted thiophenes was developed. This methodology utilizes readily available compounds in a two-step synthesis to provide a facile access to the 2,3-disubstituted thiophenes. In the...
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.