3-alkil(aril)-4-(3-etoksi-4-hidroksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on'lardan bazı yeni N-mannich bazlarının sentezi ve bazı özelliklerinin incelenmesi
Synthesis and investigation of some properties of new N-mannich bases from 3-alkyl(aryl)-4-(3-etoxy-4-hydroxy)-benzylidenamino-4,5-dihydro-1H -1,2,4-triazol-5-ones
Yazar: BAHAR BANKOĞLU YOLA
Danışman: PROF. DR. HAYDAR YÜKSEK
Kafkas Üniversitesi / Fen Bilimleri Enstitüsü / Kimya Ana Bilim Dalı
Derece: Doktora, 2021
Konu: Kimya = Chemistry

Özet:
Bu tez çalışmasında, ilk olarak literatürde kayıtlı 9 adet 3-alkil(aril)-4-amino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri elde edilerek 3-etoksi-4-hidroksibenzaldehid ile reaksiyonundan bilinen 9 adet 3-alkil(aril)-4-(3-etoksi-4-hidroksi)-benzilidenamino4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri sentezlenmiştir. Akabinde elde edilen ve
Schiff bazları olan bu bileşiklerin Mannich reaksiyonuna göre formaldehit varlığında değişik 6 adet halkalı sekunder aminle (morfolin, 2,6-dimetilmorfolin, 3-metilpiperidin, 4-piperidinkarboksamid, 1-metilpiperazin ve piperazin) muamelesinden 38 adet yeni NMannich bazı sentezlenmiştir. Sentez bölümünün ilk aşaması olan bu bölümde; 3-alkil(aril)-4-(3-etoksi-4-hidroksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşiklerinin, sırasıyla morfolin ile reaksiyonundan 8 adet yeni 1-(morfolin-4-il-metil)- 3-alkil(aril)-4-(3-etoksi-4-hidroksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri, 2,6-dimetilmorfolin ile reaksiyonundan 8 adet yeni 1-(2,6-dimetilmorfolin-4-
il-metil)-3-alkil(aril)-4-(3-etoksi-4-hidroksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri, 3-metilpiperidin ile reaksiyonundan 3 adet yeni 1-(3-metilpiperidin-1-il-metil)-3-alkil(aril)-4-(3-etoksi-4-hidroksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri, 4-piperidin karboksamid ile raksiyonundan 9 adet yeni 1-(4-aminokarbonilpiperidin-1-il-metil)-3-alkil(aril)-4-(3-etoksi-4-hidroksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri, 1-metilpiperazin ile reaksiyonundan 3 adet yeni 1-(1-metilpiperazin-4-il-metil)-3-alkil(aril)-4-(3-etoksi-4-hidroksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri ve piperazin ile
reaksiyonundan 7 adet yeni bis-[3-alkil(aril)-4-(3-etoksi-4-hidroksi)-benzilidenamino4,5-dihidro-1H-1,2,4-triazol-5-on-1-il-metil]-piperazin bileşikleri sentezlenmiştir. Tez çalışmasının sentez bölümünün devamında 3-etoksi-4-hidroksibenzaldehid'in asetik anhidrit ile reaksiyonu sonucunda oluşan 3-etoksi-4-asetoksibenzaldehitin, 3-alkil(aril)-
4-amino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri ile reaksiyonundan literatürde kayıtlı 6 adet 3-alkil(aril)-4-(3-etoksi-4-asetoksi)-benzilidenamino-4,5-dihidro-1H1,2,4-triazol-5-on bileşikleri sentezlenmiştir. Ardından sentezi yapılan bu bileşikler Mannich reaksiyonuna göre formaldehit varlığında üç farklı halkalı sekunder aminle (morfolin, 4-piperidinkarboksamid ve 1-metilpiperazin) muamele edilerek 18 adet yeni N-Mannich bazı sentezlenmiştir. Şöyle ki; 3-alkil(aril)-4-(3-etoksi-4-asetoksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşiklerinin morfolin ile
muamelesinden 6 adet yeni 1-(morfolin-1-il-metil)-3-alkil(aril)-4-(3-etoksi-4-asetoksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri, 4-piperidinkarboksamid ile muamelesinden 6 adet yeni 1-(4-aminokarbonilpiperidin-1-il-metil)-3-akil(aril)-4-(3-etoksi-4-asetoksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri ve 1-metilpiperazin ile reaksiyonundan 6 adet yeni 1-(1-metilpiperazin-4-il-metil)-3-alkil(aril)-4-(3-etoksi-4-asetoksi)-benzilidenamino-4,5-dihidro-1H-1,2,4-triazol-5-on bileşikleri sentezlenmiştir. Sentezlenen toplam 56 yeni heterosiklik bileşiğin yapıları FT-IR, 1H-NMR ve 13C-NMR tekniklerinden faydalanılarak açıklanmıştır. Çalışmanın devamında ikinci olarak, sentezlenen yeni heterosiklik bileşiklerin üç farklı yöntemle (indirgeme gücü, serbest radikal giderme aktivitesi ve metal şelat aktivitesi) in-vitro antioksidan değerlendirmeleri yapılmış ve elde edilen sonuçlar tartışılmıştır. Çalışmanın son bölümünde sentezlenen yeni bileşiklerin in-vitro antimikrobiyal etkileri agar kuyucuk yöntemi kullanılarak 5 farklı mikroorganizmaya (Bacillus cereus (ATCC 11778), Klebsiella pneumonia (ATCC 4352), Staphylococcus aureus (ATCC 6538), Serratia marcescens (ATCC 13880) ve Candida albicans (ATCC 10231)) karşı incelenmiş olup, elde edilen veriler değerlendirilmiştir

Abstract:
In this thesis, firstly, nine 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones registered in the literature were obtained and nine 3-alkyl(aryl)-4-(3-ethoxy-4-hydroxy)-benzylidenamino-4,5-dihydro-1H-1,2,4-triazole-5-ones have been synthesized from the reactions of the obtained compounds with 3-ethoxy-4-hydroxybenzaldehyde. Afterward,
according to the Mannich reaction of these compounds which were Schiff bases, were treated with 6 different cyclic secondary amines (morpholine, 2,6-dimethylmorpholine, 3-methylpiperidine, 4-piperidinecarboxamide, 1-methylpiperazine, and piperazine) in the presence of formaldehyde, and 38 new N-Mannich bases were synthesized. Namely, in this section which is the first stage of the synthesis section; 3-alkyl(aryl)-4-(3-ethoxy4-hydroxy)-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones; by reacting with morpholine 8 new 1-(morpholin-4-yl-methyl)-3-alkyl(aryl)-4-(3-ethoxy-4-hydroxy)-
benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones, by reacting with 2,6-dimethylmorpholine 8 new 1-(2,6-dimethylmorpholin-4-yl-methyl)-3-alkyl(aryl)-4-(3-ethoxy-4-hydroxy)-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones, by reacting with 3-methylpiperidine 3 new 1-(3-methylpiperidin-1-yl-methyl)-3-alkyl(aryl)-4-(3-ethoxy-4-hydroxy)-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones, by reacting with 4-aminocarbonylpiperidine 9 new 1-(4-aminocarbonylpiperidin-1-yl-methyl)-3-alkyl(aryl)-4-(3-ethoxy-4-hydroxy)-benzyliden-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones, by reacting with 1-methylpiperazine 3 new 1-(1-methylpiperazine-4-yl-methyl)-3-alkyl(aryl)-4-(3-ethoxy-4-hydroxy)-benzyliden-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones and by reacting with piperazine 7 new bis-[3-alkyl(aryl)-4-(3-ethoxy-4-hydroxy)-benzylideneamino-4,5-dihydro-1H-1,2,4-triazol-5-on-1-yl-methyl]-piperazines were
synthesized, respectively. In the continuation of the synthesis part of the thesis, six 3-alkyl(aryl)-4-(3-ethoxy-4-
acetoxy)-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-one compounds registered in the literature were synthesized by the reactions with 3-alkyl(aryl)-4-amino-4,5-dihydro1H-1,2,4-triazole-5-one and 3-ethoxy-4-acetoxybenzaldehyde which formed with the reaction of 3-ethoxy-4-hydroxybenzaldehyde and acetic anhydride. Then, these synthesized compounds were treated with three different cyclic secondary amines (morpholine, 4-piperidinecarboxamide and 1-methylpiperazine) in the presence of formaldehyde according to the Mannich reaction, and 18 new N-Mannich bases were synthesized. So 3-alkyl(aryl)-4-(3-ethoxy-4-acetoxy)-benzylidenamino-4,5-dihydro-1H1,2,4-triazol-5-one compounds; by reacting with morpholine 6 new 1-(morpholin-1-ylmethyl)-3-alkyl(aryl)-4-(3-ethoxy-4-acetoxy)-benzylideneamino-4,5-dihydro-1H-1,2,4-
triazol-5-ones, by reacting with 4-piperidinecarboxamide 6 new 1-(4-aminocarbonylpiperidin-1-yl-methyl)-3-alkyl(aryl)-4-(3-ethoxy-4-acetoxy)-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones and by reacting with 1-methylpiperazine 6 new 1-(1-methylpiperazine-4-yl-methyl)-3-alkyl(aryl)-4-(3-ethoxy4-acetoxy)-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones were synthesized, respectively. The structures of a total of 56 new heterocyclic compounds synthesized were elucidated using FT-IR, 1H-NMR and 13C-NMR techniques. In the continuation of the study, in-vitro antioxidant evaluations of the synthesized new compounds with three different methods (reducing power, free radical scavenging
activity, and metal chelating activity) were made and the obtained results were discussed. In the final section, the in-vitro antimicrobial effects of the newly synthesized heterocyclic compounds were screened to 5 different microorganisms (Bacillus cereus (ATCC 11778), Klebsiella pneumonia (ATCC 4352), Staphylococcus aureus (ATCC 6538), Serratia marcescens (ATCC 13880) and Candida albicans (ATCC 10231)) and the data obtained were evaluated.