Beş üyeli heterosiklik bileşikler üzerine bir çalışma
A study on five-membered heterocyclic compounds
Yazar: SEVİLAY DEMİRCİ
Danışman: PROF. DR. HAYDAR YÜKSEK
Kafkas Üniversitesi / Fen Bilimleri Enstitüsü / Kimya Ana Bilim Dalı
Derece: Doktora, 2011
Konu: Kimya = Chemistry

Özet:
Bu tez çalışmasında 52 adet potansiyel biyolojik aktif 4,5-dihidro-1H-1,2,4-triazol-5-on türevi elde edilmiş, yapıları aydınlatılmış ve antioksidan özellikleri ile asidik NH grubu içeren bileşiklerin pKa değerleri tayin edilmiştir.Çalışmada ilk olarak 3-alkil(aril)-4-amino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri sentezlenerek tez kapsamında elde edilmiş olan ve birer benzaldehid türevleri olan 3-etoksi-4-(3-nitrobenzoksi)benzaldehid, 3-etoksi-4-(3,5-dinitrobenzoksi)benzaldehid ve 3-asetoksi-5-bromobenzaldehid ile reaksiyonları incelenmiş ve karşın olan, sırasıyla 3-alkil(aril)-4-[3-etoksi-4-(3-nitrobenzoksi)-benzilidenamino]-4,5-dihidro-1H-1,2,4-triazol-5-on, 3-alkil(aril)-4-[3-etoksi-4-(3,5-dinitrobenzoksi)-benzilidenamino]-4,5-dihidro-1H-1,2,4-triazol-5-on ve 3-alkil(aril)-4-(2-asetoksi-5-bromobenzilidenamino)-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri elde edilmiştir. Bu bileşiklerin asetik anhidrid ile reaksiyonundan N-asetil türevleri elde edilmiştir. Ayrıca 3-alkil(aril)-4-(3-etoksi-4-hidroksi)benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşiklerinin benzil bromür ve fenasil bromür ile de reaksiyonları incelenmiş ve sırasıyla 3-alkil(aril)-4-(3-etoksi-4-fenilmetoksibenzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on ve 1-fenasil-3-alkil(aril)-4-(3-etoksi-4-benzoilmetoksi)benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri sentezlenmiştir. Çalışmanın sentez bölümünde son olarak 3-benzil-4-(3-etoksi-4-hidroksibenzilidenamino)-4,5-dihidro-1H-1,2,4-triazol-5-on bileşiğinden başlayarak 1-etoksikarbonilmetil-3-benzil-4-(3-etoksi-4-etoksikarbonilmetoksi)benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşiği üzeriden bir dihidrazid olan 1-hidrazinokarbonilmetil-3-benzil-4-(3-etoksi-4-hidrazinokarbonilmetoksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on [3-benzil-4-(3-etoksi-4-hidrazinokarbonilmetoksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on-1-il]-asetohidrazid bileşiği elde edilmiş ve bazı reaksiyonları incelenmiştir. Bu amaçla ilk olarak dihidrazidin 4-metoksibenzaldehid, 4-hidroksibenzaldehid, 3-hidroksi-4-metoksibenzaldehid ve salisilaldehid ile reaksiyonundan sırasıyla 1-(4-metoksibenzilidenhidrazinokarbonilmetil)-3-benzil-4-[3-etoksi-4-(4-metoksibenziliden hidrazinokarbonilmetoksi)-benzilidenamino]-4,5-dihidro-1H-1,2,4-triazol-5-on, 1-(4-hidroksibenzilidenhidrazinokarbonilmetil)-3-benzil-4-[3-etoksi-4-(4-hidroksibenziliden hidrazinokarbonilmetoksi)-benzilidenamino]-4,5-dihidro-1H-1,2,4-triazol-5-on, 1-(3-hidroksi-4-metoksibenzilidenhidrazinokarbonilmetil)-3-benzil-4-[3-etoksi-4-(3-hidroksi -4-metoksibenzilidenhidrazinokarbonilmetoksi)-benzilidenamino]-4,5-dihidro-1H-1,2,4-triazol-5-on ve 1-(2-hidroksibenzilidenhidrazinokarbonilmetil)-3-benzil-4-[3-etoksi-4-(2-hidroksibenzilidenhidrazinokarbonilmetoksi)-benzilidenamino]-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri elde edilmiştir. Ayrıca asetonilaseton ve suksindialdehid vericisi 2,5-dimetoksiterahidrofuran ile de reaksiyonları incelenerek 1-[(2,5-dimetilpirrol-1-il)aminokarbonilmetil]-3-benzil-4-[3-etoksi-4-(2,5-dimetilpirrol-1-il)-aminokarbonilmetoksibenzilidenamino]-4,5-dihidro-1H-1,2,4-triazol-5-on ve 1-[(pirrol-1-il)aminokarbonilmetil]-3-benzil-4-[3-etoksi-4-(pirrol-1-il)-aminokarbonil metoksibenzilidenamino]-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri sentezlenmiştir. Bu bölümde son olarak dihidrazidin fenilizotiyosiyanat ile reaksiyonundan 1-(feniltiyoüreidokarbamoilmetil)-3-benzil-4-[3-etoksi-4-(feniltiyoüreido-karbamoil metoksibenzilidenamino)]-4,5-dihidro-1H-1,2,4-triazol-5-on ve potasyum hidroksitli ortamda CS2 ile reaksiyonundan 1-(4,5-dihidro-1,3,4-oksadiazol-5-tion-2-il)metil-3-benzil-4-[3-etoksi-4-(4,5-dihidro-1,3,4-oksadiazol-5-tion-2-il)metoksibenzilidenamino]-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri oluşturulmuştur.Çalışmanın ikinci bölümünde 3'ü benzaldehid türevi olmak üzere sentezlenen 55 yeni bileşiğin yapıları IR, 1H-NMR ve 13C-NMR spektroskopik yöntemleri ile mikroanaliz kullanılarak aydınlatılmıştır.Çalışmanın üçüncü bölümünde zayıf asidik NH grubuna sahip 23 yeni bileşiğin 4 farklı susuz çözücüde (izopropil alkol, tert-butil alkol, N,N-dimetilformamid ve aseton) tetrabutilamonyumhidroksit ile potansiyometrik olarak titrasyonları yapılmış, titrasyon grafikleri çizilmiş, yarı nötralizasyon metodu ile yarı nötralizasyon potansiyelleri ve karşın olan pKa değerleri tayin edilmiştir. Elde edilen sonuçlardan yararlanarak asitlik üzerine çözücü ve molekül yapısının etkisi tartışılmıştır.Tez kapsamında son olarak sentezlenen 52 yeni bileşiğin üç farklı yöntemle (indirgeme gücü, serbest radikal giderme aktivitesi ve metal şelat aktivitesi) antioksidan aktiviteleri incelenmiş, grafikleri çizilmiş ve sonuçlar yorumlanmıştır.

Abstract:
In the first part of this study, 52 potentially bio-active 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives were synthesized, and their molecular structures were characterized. Then, in the second and third parts of the study, antioxidant properties of all compounds, and pKa values of the compounds that contain acidic NH group were determined.Initially, 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones were synthesized and their reactions with 3-ethoxy-4-(3-nitrobenzoxy)benzaldehyde, 3-ethoxy-4-(3,5-dinitrobenzoxy)benzaldehyde, 3-acetoxy-5-bromobenzaldehyde synthesized which are benzaldehyde derivatives were investigated. These reactions resulted in corresponding compounds: 3-alkyl(aryl)-4-[3-ethoxy-4-(3-nitrobenzoxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones, 3-alkyl(aryl)-4-[3-ethoxy-4-(3,5-dinitrobenzoxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones, and 3-alkyl(aryl)-4-(2-asetoxy-5-bromobenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones, respectively. From the reactions of these compounds with acetic anhydride, their N-acetyl derivatives were obtained. In addition, the reactions of 3-alkyl(aryl)-4-(3-ethoxy-4-hidroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones with benzyl bromide and fenacyl bromide were also investigated and 3-alkyl(aryl)-4-(3-ethoxy-4-phenylmetoxybenzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones and 1-fenacyl-3-alkyl(aryl)-4-(3-ethoxy-4-benzoylmethoxy)-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones were synthesized, respectively. In the synthesis part of the study, finally, starting from the compound, 3-benzyl-4-(3-ethoxy-4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-one, and passing through the intermediate product, 1-ethoxycarbonylmethyl-3-benzyl-4-(3-ethoxy-4-ethoxycarbonylmethoxybenzyliden-amino-4,5-dihydro-1H-1,2,4-triazol-5-one, the compound 1-hydrazinocarbonylmethyl-3-benzyl-4-(3-ethoxy-4-hydrazinocarbonylmethoxy)-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one, [3-benzyl-4-(3-ethoxy-4-hydrazinocarbonylmethoxy)-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one-1yl]- acetohydrazide which is a dihydrazide was synthesized, and its some reactions were investigated. For this purpose, first of all, from the reactions of the dihydrazide with 4-metoxybenzaldehyde, 4-hydroxybenzaldehyde, 3-hydroxy-4-methoxybenzaldehyde and salicylaldehyde, 1-(4-methoxybenzylidenhydrazinocarbonylmethyl)-3-benzyl-4-[3-ethoxy-4-(4-methoxy-benzylidenhydrazinocarbonylmethoxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-one, 1-(4-hyroxybenzylidenhydrazinocarbonylmethyl)-3-benzyl-4-[3-ethoxy-4-(4- hydroxybenzylidenhydrazinocarbonylmethoxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-one, 1-(3-hydroxy-4-methoxybenzylidenhydrazinocarbonylmethyl)-3-benzyl-4-[3-ethoxy-4-(3-hydroxy-4-methoxybenzylidenhydrazinocarbonylmethoxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-one and 1-(2-hyroxybenzyliden-hydrazinocarbonylmethyl)-3-benzyl-4-[3-ethoxy-4-(2-hydroxybenzylidenhydrazino-carbonylmethoxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-one compounds were obtained, respectively. Besides, its reactions with acetonylacetone and 2,5-dimethoxytetrahydrofuran as succindialdehyde donor were also investigated. Thus, 1-[(2,5-dimethylpirrol-1-yl)aminocarbonylmethyl]-3-benzyl-4-[3-ethoxy-4-(2,5-dimethylpirrol-1-yl)-aminocarbonylmethoxybenzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-one and 1-[(pirrol-1-yl)aminocarbonylmethyl]-3-benzyl-4-[3-ethoxy-4-(pirrol-1-yl)-aminocarbonylmethoxybenzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-one compounds were synthesized. In this part, eventually, from the reactions of the dihydrazide with phenylisothiocyanate, and in the presence of potassium hydroxide with CS2, 1-(phenylthioureidocarbamoylmethyl)-3-benzyl-4-[3-ethoxy-4-(phenylthioureido-carbamoylmethoxybenzylidenamino)]-4,5-dihydro-1H-1,2,4-triazol-5-one and 1-(4,5-dihydro-1,3,4-oxadiazole-5-thione-2-yl)methyl-3-benzyl-4-[3-ethoxy-4-(4,5-dihydro-1,3,4-oxadiazole-5-thione-2-yl)methoxybenzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-one compounds were formed.In the second part of the study, the molecular structures of 55 newly synthesized compounds, three of which were benzaldehyde derivatives, were identified by using IR, 1H-NMR, 13C-NMR, and microanalysis techniques.In the third part of the study, potentiometric titrations of 23 new compounds that contain acidic NH group were carried out in four different non-aqueous solvents (isopropyl alcohol, tert-buthy alcohol, N,N-dimethylformamide and acetone). In order to determine their half neutralization potentials and pKa values according to the half neutralization method, their titration graphs were drawn. The effects of molecular structures and solvents upon acidity were examined and discussed.Finally, 52 compounds synthesized were subject to analysis for their antioxidant activities by using different methods such as reducing power, free radical scavenging, and metal chelating activity. In each method, related graphics were drawn and interpreted.