Sinteza i spektroskopska karakterizacija novih amino supstituiranih derivata benzimidazo[1,2-a]kinolina katalitičkom aminacijom

master's thesis

• Title (english): Synthesis and spectroscopic characterization of novel amino substituted benzimidazo[1,2-a]quinolones by catalytic amination
• Author: Marija Kos
• Mentor: Marijana Hranjec (mentor)
• Committee member: Marijana Hranjec (predsjednik povjerenstva)
• Committee member: Tatjana Gazivoda Kraljević (član povjerenstva)
• Committee member: Dragana Mutavdžić Pavlović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2020-09-11, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U okviru ovog rada provedena je sinteza, optimizacija reakcijskih uvjeta te spektroskopska karakterizacija nastalih produkata dobivenih pri pokušaju sinteze novih aminskih derivata benzimidazo[1,2-a]kinolin-6-karbonitrila. Spojevi su priređeni klasičnim reakcijama organske sinteze te mikrovalovima potpomognutom sintezom. U reakcijama katalitičke Buchwald-Hartwigove aminacije korišten je fosfinski ligand treće generacije. Aciklički prekursor 4 priređen je reakcijom kondenzacije acetonitrila 2 i o-klorbenzaldehida 3, a njegovom termičkom ciklizacijom u sulfolanu pri 280 ºC dobiveni su tetraciklički derivati benzimidazo[1,2-a]kinolina 5a i 5b. Regioizomeri 5a i 5b razdvojeni su kolonskom kromatografijom na silikagelu uz diklormetan kao eluens. Buchwald-Hartwigovom reakcijom aminacije regioizomera 5a i 5b s izobutilaminom proveden je pokušaj sinteze ciljanih amino supstituiranih derivata benzoimidazo[1,2-a]kinolina 6a i 6b. Kako bi se optimirali reakcijski uvjeti, promijenjeni su vrijeme reakcije i vrsta baza te je sinteza provedena termički i pomoću mikrovalova, no željeni spojevi nisu uspješno sintetizirani. Strukture svih prekursora potvrđene su 1H i 13C NMR spektroskopijom dok su strukture dobivenih produkata analizirane masenom spektrometrijom te neke dodatno 1H, 13C i 2D NMR spektroskopijom.

Abstract (english)

This work presents the synthesis, optimisation of reaction conditions and spectroscopic characterisation of the resulting products obtained in an attempt to synthesize novel amino substituted benzimidazo[1,2-a]quinoline-6-carbonitrile derivates. All compounds were prepared by conventional reactions of organic chemistry and microwave assisted synthesis. A third generation of phosphine ligand was used in the catalytic Buchwald-Hartwig amination reactions. Acyclic precursor 4 was prepared by the condensation reaction of acetonitrile 2 and o-chlorobenzaldehyde 3. By its thermal cyclization reaction in sulfolane at 280 ºC tetracyclic derivates of benzimidazo[1,2-a]quinolines 5a and 5b were obtained. Regioisomers 5a and 5b were successfully separated by column chromatography on silicagel by using dichloromethane as an eluent. Buchwald-Hartwig amination of regioisomers 5a and 5b with isobutylamine was used in an attempt to prepare targeted amino substituted benzimidazo[1,2-a]quinoline derivates 6a i 6b. In order to optimize the reaction conditions, the reaction time and base were changed. Also the synthesis was carried out thermally and using microwaves, but the desired compounds were not successfully synthesized. The structures of all precursors were confirmed by means of 1H and 13C NMR spectroscopy, while the structures of the obtained products were characterized by mass spectrometry and some additionally by 1H, 13C and 2D NMR spectroscopy.

• Keywords: benzimidazoli; benzimidaz[1 2-a]kinolini; katalitička Buchwald-Hartwigova aminacija; 1H i 13C NMR spektroskopija; masena spektrometrija
• Keywords (english): benzimidazoles; benzimidazo[1 2-a]quinolines; catalytic Buchwald-Hartwig amination; 1H i 13C NMR spectroscopy; mass spectrometry
• Language: croatian
• URN:NBN: urn:nbn:hr:149:442561
• Project: Number: IP-2018-01-4379; Title: Istraživanje antioksidativnog djelovanja benzazolskog skeleta u dizajnu novih antitumorskih agensa; Acronym: AntioxPot; Leader: Marijana Hranjec; 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: Access restricted to students and staff of home institution
• Created on: 2022-03-05 10:00:04