Sinteza, strukturna karakterizacija i antibakterijsko djelovanje novih 2-hidrazonskih derivata benzotiazola

master's thesis

• Title (english): Synthesis, structural characterization and antibacterial activity of novel 2-hydrazone derivatives of benzothiazole
• Author: Hanja Mlinar
• Mentor: Tatjana Gazivoda Kraljević (mentor)
• Committee member: Tatjana Gazivoda Kraljević (predsjednik povjerenstva)
• Committee member: Silvana Raić-Malić (član povjerenstva)
• Committee member: Dajana Kučić Grgić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2022-09-13, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom radu opisana je sinteza ciljanih derivata benzotiazola premoštenih hidrazonskom spojnicom (3-14) i 1,2,3-triazolnih derivata benzotiazola (17-26) kao potencijalno biološki aktivnih agenasa te je provedena njihova strukturna karakterizacija spektroskopijom NMR. 2-amino-6-metoksibenzo[d]tiazol (1) sintetiziran je reakcijom ciklizacije p-metoksianilina s kalijevim tiocijanatom i bromom u octenoj kiselini koji je potom reakcijom nukleofilne supstitucije s hidrazin hidratom u prisustvu etilen-glikola i klorovodične kiseline preveden u 2-hidrazinil-6-metoksibenzo[d]tiazol (2). Benzotiazolni derivati hidrazona (3-14) pripremljeni su mehanokemijskim reakcijama 2-hidrazinil-6-metoksibenzo[d]tiazola (2) i odgovarajućih aldehida. Mikrovalovima potpomognutom reakcijom O-alkiliranja 3-hidroksi-4-metoksibenzaldehida s propargil-bromidom i kalijevim karbonatom kao bazom sintetiziran je 4-metoksi-3-(prop-2-in-1-iloksi)benzaldehid (15). Reakcijom kondenzacije spoja 15 i 2-aminotiofenola uz natrijev metabisulfit kao oksidacijsko sredstvo u dimetilformamidu pripravljen je 2-(4-metoksi-3-(prop-2-in-1-iloksi)fenil)benzo[d]tiazol (16). 1,2,3-triazolni derivati benzotiazola (17-26) sintetizirani su mehanokemijskom Huisgenovom 1,3-dipolarnom cikloadicijom spoja 16 i odgovarajućih azida u metanolu uz bakrov(II) acetat kao katalizator. Strukturna karakterizacija priređenih spojeva provedena je spektroskopijom 1H i 13C-NMR. In silico analizom predviđeni su farmakološki učinci i moguće biološke mete pripravljenih spojeva.

Abstract (english)

In this paper, the synthesis of targeted benzothiazole derivatives bridged with a hydrazone coupling (3-14) and 1,2,3-triazole benzothiazole derivatives (17-26) as potentially biologically active agents is described, and their structural characterization by NMR spectroscopy was carried out. 2-amino-6-methoxybenzo[d]thiazole (1) was synthesized by the cyclization reaction of pmethoxyaniline with potassium thiocyanate and bromine in acetic acid, which was then converted into 2-hydrazinyl-6-methoxybenzo[d]thiazole (2) by reaction of nucleophilic substitution with hydrazine hydrate in the presence of ethylene glycol and hydrochloric acid. Benzothiazole hydrazone derivatives (3-14) were prepared by mechanochemical reactions of 2-hydrazinyl-6-methoxybenzo[d]thiazole (2) and corresponding aldehydes. 4-methoxy-3-(prop-2-yn-1-yloxy)benzaldehyde (15) was synthesized by microwave-assisted reaction of O-alkylation of 3-hydroxy-4-methoxybenzaldehyde with propargyl bromide and potassium carbonate as a base. 2-(4-methoxy-3-(prop-2-yn-1-yloxy)phenyl)benzo[d]thiazole (16) was prepared by the condensation reaction of compound 15 and 2-aminothiophenol with sodium metabisulfite as an oxidizing agent in dimethylformamide. 1,2,3-triazole derivatives of benzothiazole (17-26) were synthesized by mechanochemical Huisgen 1,3-dipolar cycloaddition of compound 16 and the corresponding azides in methanol with copper(II) acetate as a catalyst. Structural characterization of the prepared compounds was performed by 1H and 13C-NMR spectroscopy. Pharmacological effects and possible biological targets of the prepared compounds were predicted by in silico analysis.

• Keywords: benzotiazol; hidrazon; 1 2 3-triazol; klik reakcija; mehanokemijske reakcije
• Keywords (english): benzothiazole; hydrazone; 1 2 3-triazole; click reaction; mechanochemical reactions
• Language: croatian
• URN:NBN: urn:nbn:hr:149:759034
• Project: Number: IP-2018-01-4682; Title: Novi spojevi temeljeni na bioizosterima purina za ispitivanje njihovih antitumorskih i antipatogenih djelovanja; Acronym: PurBioCaPa; Leader: Silvana Raić-Malić; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry; Course: Applied organic chemistry; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Closed access
• Created on: 2023-03-19 17:03:31