4,5-dihidro-1H-1,2,4-triazol-5-on halkası içeren bazı yeni heterosiklik mannich bazlarının sentezi, karakterizasyonu ve bazı özelliklerinin incelenmesi
Synthesis, characterization and investigation of some properties of some new heterocyclic mannich bases with 4,5-dihidro-1H-1,2,4-triazol-5-one ring
Yazar: FEVZİ AYTEMİZ
Danışman: PROF. DR. HAYDAR YÜKSEK
Kafkas Üniversitesi / Fen Bilimleri Enstitüsü / Kimya Ana Bilim Dalı / Organik Kimya Bilim Dalı
Derece: Doktora, 2020
Konu: Kimya = Chemistry

Özet:
Bu çalışmada, öncelikle çalışma için gerekli olan 9 adet 3-alkil/aril-4-amino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşiği sentezlenmiştir. Sonra salisilaldehit (2-hidroksibenzaldehit), 3-hidroksibenzaldehit ve 3-hidroksi-4-metoksibenzaldehit soğukta trietilamin varlığında 2,5-diklorobenzensulfonil klorür ile muamele edilerek literatürde kayıtlı 2-formilfenil 2,5-diklorobenzensulfonat, yeni 3-formilfenil 2,5-diklorobenzensulfonat ve 2-metoksi-5-formilfenil 2,5-diklorobenzensulfonat bileşikleri elde edilmiştir. Daha sonra bu substitue-benzaldehid türevlerinin 3-alkil/aril-4-amino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri ile muamelesinden 27 adet yeni 2-[(3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il)-azometin]-fenil 2,5-diklorobenzensulfonat, 3-[(3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il)-azometin]-fenil 2,5-diklorobenzensulfonat ve 2-metoksi-5-[(3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il)-azometin]-fenil 2,5-diklorobenzensulfonat bileşikleri sentezlenmiştir. Sentezi gerçekleştirilen bileşikler Mannich reaksiyonu uyarınca formaldehit varlığında morfolin, 3-metilpiperidin ve piperidin-4-karboksamid ile muamele edilerek sırasıyla 5 adet yeni 2-{[1-(morfolin-4-il-metil)-3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il]-azometin}-fenil 2,5-diklorobenzensulfonat, 5 adet yeni 3-{[1-(morfolin-4-il-metil)-3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il]-azometin}-fenil 2,5-diklorobenzensulfonat, 6 adet yeni 3-{[1-(3-metilpiperidin-1-il-metil)-3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il]-azometin}-fenil 2,5-diklorobenzensulfonat, 5 adet yeni 3-{[1-(piperidin-4-karboksamid-1-il-metil)-3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il]-azometin}-fenil 2,5-diklorobenzensulfonat 5 adet yeni 2-metoksi-5-{[1-(morfolin-4-il-metil)-3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il]-azometin}-fenil 2,5-diklorobenzensulfonat ve 5 adet yeni 2-metoksi-5-{[1-(3-metilpiperidin-1-il-metil)-3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il]-azometin}-fenil 2,5-diklorobenzensulfonat olmak üzere toplam 31 adet Mannich bazı elde edilmiştir.

İkinci bölümde sentezlenen 1'i literatürde kayıtlı toplam 61 bileşiğin yapıları IR, 1H-NMR, 13C-NMR ve kütle spektroskopik yöntemleri kullanılarak aydınlatılmıştır.

Çalışmanın üçüncü bölümünde yeni bileşiklerin in-vitro antimikrobiyal özellikleri agar kuyucuk difuzyon yöntemi ile 6 farklı mikroorganizmaya karşı incelenmiştir. 

Dördüncü bölümünde sentezlenen yeni bileşiklerin indirgeme gücü, serbest radikal giderme aktivitesi ve metal şelat aktivitesi yöntemleriyle in-vitro antioksidan özellikleri incelenmiş ve elde edilen sonuçlar kullanılan standart antioksidan bileşiklerle mukayese edilmiştir.

Tez çalışmasının son bölümünde zayıf asidik N-H grubu taşıyan yeni bileşiklerin 4 farklı susuz çözücüde (izopropil alkol, tert-butil alkol, aseton ve N,N-dimetilformamid) tetrabutilamonyum hidroksit (TBAH) ile potansiyometrik olarak titrasyonları yapılarak yarı nötralizasyon metodu ile pKa değerleri bulunmuştur.

Abstract:
In this study, initially nine 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-one compounds required for the study were synthesized. Later, 2-formylphenyl 2,5-dichlorobenzenesulfonate in the literature, new 3-formylphenyl 2,5-dichlorobenzenesulfonate and 2-methoxy-5-formylphenyl 2,5-dichlorobenzenesulfonate were obtained by treating salicylaldehyde (2-hydroxybenzaldehyde), 3-hydroxybenzaldehyde and 3-hydroxy-4-methoxybenzaldehyde with 2,5-dichlorobenzenesulfonyl chloride in the presence of triethylamine in the cold. Following the treatment of these substituted-benzaldehyde derivatives with 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones compounds, 27 new 2-[(3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl)-azomethine]-phenyl 2,5-dichlorobenzenesulfonate, 3-[(3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl)-azomethine]-phenyl 2,5-dichlorobenzenesulfonate and 2-methoxy-5-[(3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl)-azomethine]-phenyl 2,5-dichlorobenzenesulfonate compounds were synthesized. Synthesized compounds were treated with morpholine, 3-methylpiperidine and piperidine-4-carboxamide in the presence of formaldehyde in accordance with the Mannich reaction, and respectively 5 new 2-{[1-(morpholin-4-yl-methyl)-3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl 2,5-dichlorobenzenesulfonates, 5 new 3-{[1-(morpholin-4-yl-methyl)-3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazole-5-on-4-yl]-azomethine}-phenyl 2,5-dichlorobenzenesulfonates, 6 new 3-{[1-(3-methylpiperidin-1-yl-methyl)-3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl 2,5-dichlorobenzenesulfonates, 5 new 3-{[1-(piperidine-4-carboxamide-1-yl-methyl)-3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl 2,5-dichlorobenzenesulfonates, 5 new 2-methoxy-5-{[1-(morpholin-4-yl-methyl)-3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-one-4-yl]-azomethine}-phenyl 2,5-dichlorobenzenesulfonates and 5 new 2-methoxy-5-{[1-(3-methylpiperidin-1-yl-methyl)-3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-one-4-il]-azomethine}-phenyl 2,5-dichlorobenzenesulfonates were obtained with a total number of 31 Mannich bases.

The structures of 61, one in the literature, compounds as synthesized in the second part were characterized by using IR, 1H-NMR, 13C-NMR and mass spectroscopic methods.

In the third part of the study, the in-vitro antimicrobial properties of the new compounds were investigated against 6 different microorganisms by the agar well diffusion method.

In the fourth section, the in-vitro antioxidant properties of the novel compounds were investigated using the methods of reduction power, free radical scavenging activity and metal chelating activity, and the results were compared with the standard antioxidants.

In the last part of the thesis, pKa values were determined by the half-neutralization method through potentiometric titration of new compounds carrying weak acidic N-H group with tetrabutylammonium hydroxide (TBAH) in 4 different non-aqueous solvents (isopropyl alcohol, tert-butyl alcohol, acetone and N,N-dimethylformamide).