Synthesis of highly substituted alkynylpyridines and development of new methodologies for the synthesis of 1,4-oxazepines, 1,4-thiazepines and 5-methylpyridines /

Download
2018
Kelgökmen, Yılmaz
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 of 5-iodopyridines by iodine-mediated electrophilic cyclization reaction. Accordingly, in this thesis work, the first aim is to further functionalize 5-iodopyridines by utilizing Sonogashira cross-coupling reaction. With this way, we have synthesized 28 new 5-alkynylpyridines in 40-99% yields. Secondly, for the synthesis of 1,4-oxazepines, we have reinvestigated ZnCl2-mediated 7-exo-dig cyclization in refluxing CHCl3 to get higher yields in shorter reaction durations. Thus, we have achieved the smooth synthesis of many 2-methylene-2,3-dihydro-1,4-oxazepine derivatives in good to high yields (66-95%) in 1.5-12.0 h. In some cases, conversion of alkyl-substituted 1,4-oxazepines to the corresponding pyrrole derivatives has been observed to some extent during their isolation on silica gel. In the third part of the thesis work, we have prepared novel starting N-propargylic thio-β-enaminones from the corresponding N-propargylic β-enaminone precursors by using Lawesson's reagent (LR). Then, we have examined the cyclization reactions of these thio-β-enaminones by using ZnCl2 in refluxing CHCl3. We have synthesized 20 novel 2-methylene-2,3-dihydro-1,4-thiazepines in 67-90% yields by using this unprecedented synthetic methodology. Finally, base-catalyzed cyclization reactions of N-propargylic thio-β-enaminones have been investigated, which afforded methyl-substituted pyridines via sulfur extrusion. Accordingly, in the presence of diisopropylamine (DIPA) at room temperature, many alkylpyridines have been synthesized in moderate to high yields (46-85%), except for one derivative (13%).

Suggestions

Synthesis of alkynyl-substituted pyrrole and 1,4-thiazepine derivatives
Yılmaz, Elif Serel; Zora, Metin; Department of Chemistry (2018)
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 t...
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...
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 and enzymatic resolution of various cyclopentenoid and cyclohexenoid type compounds
İyigün, Çiğdem; Tanyeli, Cihangir; Department of Chemistry (2005)
The aim of this thesis is to synthesize enantiomerically enriched cyclopentenoid and cyclohexenoid type of compounds with quaternary carbon stereocenters that are the simplest precursors of the complex natural products. The first part of the study involves the preparation of ?'-acetoxy ?'-substituted ?,β-unsaturated cyclic ketones. Methylation, ethylation, benzylation and allylation of cyclohexenone and cyclopentenone derivatives are performed. Then, these compounds are regioselectively oxidized at the ?'-p...
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...
Citation Formats
Y. Kelgökmen, “Synthesis of highly substituted alkynylpyridines and development of new methodologies for the synthesis of 1,4-oxazepines, 1,4-thiazepines and 5-methylpyridines /,” Ph.D. - Doctoral Program, Middle East Technical University, 2018.